Identification of alternatively spliced GRIM-19 mRNA in kidney cancer tissues.

Gene associated with Retinoid-Interferon-induced Mortality (GRIM)-19 was originally identified as a regulatory gene necessary for interferon-beta and retinoic acid-induced cell death. Further studies revealed that GRIM-19 is a subunit of mitochondrial respiratory chain complex I. Previous studies show that the expression of GRIM-19 is lost or severely depressed in a number of primary renal cell carcinomas (RCCs) and in some urinogenital tumors. Four point mutations were found in the GRIM-19 gene in mitochondria-rich (Hürthle) tumors and one point mutation was reported in RCC. In this study, we report an alternatively splicing form of GRIM-19 mRNA with intron 3 by reverse transcriptase PCR. This splicing variant is found in kidney tumor tissues but not in matched normal tissues. Furthermore, we found that in addition to GRIM-19, the protein level of NDUFS3, which is another mitochondrial complex I subunit, was also diminished in kidney tumor tissues when compared with paired normal tissues. Our finding suggested that the alternative splicing form of GRIM-19 is tumor tissue specific.